DESCRIPTION (adapted from the application) The current approach to vascular access in dialysis patients consists of monitoring grafts and fistulas for evidence of stenosis, and intervening to correct the stenosis after it occurs. A pharmacologic intervention that prevents vascular access complications may markedly decrease the need for salvage procedures, access-related hospitalizations, and the overall cost of caring for hemodialysis patients. Plasma homocysteine levels are frequently elevated in dialysis patients. Hyperhomocysteinemia is a risk factor for cardiovascular disease in hemodialysis patients, and may also be a risk factor for vascular access thrombosis. Folate is a substrate for homocysteine, and folic acid administration can lower homocysteine levels. Whereas standard doses of folic acid (1 mg daily) have a minimal effect on homocysteine levels in dialysis patients, pharmacologic doses (15 mg daily) can reduce homocysteine levels substantially. It is not known whether aggressive reduction of homocysteine levels in dialysis patients with pharmacologic doses of folic acid can decrease the frequency of vascular access stenosis and thrombosis. The following hypotheses will be tested in this study: (1) Pharmacologic doses of folic acid (15 mg daily) are more effective than standard doses (1 mg daily) in decreasing the frequency of graft stenosis and thrombosis in hemodialysis patients. (2) This beneficial effect of high-dose folic acid on graft outcome is proportionate to the magnitude of reduction in plasma homocysteine. (3) High dose folic acid administration is effective in improving graft outcomes both as primary prophylaxis (no previous stenosis or thrombosis) and as secondary prophylaxis (prevention of recurrent stenosis or thrombosis after an initial event). The study design is a prospective, randomized, double-blind, multicenter investigation in which chronic hemodialysis patients with AV grafts will be randomized to receive either high (15 mg daily) or standard (1 mg daily) doses of folic acid supplements. The primary endpoint will be overall graft survival. Secondary endpoints will be the frequency of graft interventions and cardiovascular events. The results will be analyzed to determine whether there are significant differences in graft survival or complications between the groups receiving high dose and standard dose of folic acid.